| 1. |
- Collingwood, T N, et al.
(författare)
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A natural transactivation mutation in the thyroid hormone beta receptor: impaired interaction with putative transcriptional mediators.
- 1997
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 0027-8424. ; 94:1, s. 248-53
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Tidskriftsartikel (refereegranskat)abstract
- The syndrome of resistance to thyroid hormone is characterized by elevated serum free thyroid hormones, failure to suppress pituitary thyrotropin secretion, and variable peripheral refractoriness to hormone action. Here we describe a novel leucine to valine mutation in codon 454 (L454V) of the thyroid hormone beta receptor (TR beta) in this disorder, resulting in a mutant receptor with unusual functional properties. Although the mutant protein binds ligand comparably to wild-type receptor and forms homo- and heterodimers on direct repeat, everted repeat, or palindromic thyroid response elements, its ability to activate transcription via these elements is markedly impaired. The hydrophobic leucine residue lies within an amphipathic alpha-helix at the carboxyl terminus of TR beta and the position of the homologous residue in the crystal structure of TR alpha indicates that its side chain is solvent-exposed and might interact with other proteins. We find that two putative transcriptional mediators (RIP140 and SRC-1) exhibit hormone-dependent association with wild-type TR. In comparison, the interaction of this natural mutant (L454V) and artificial mutants (L454A, E457A) with RIP140 and SRC-1 is markedly reduced. Furthermore, coexpression of SRC-1 is able to restore the transcriptional activity of the L454V mutant receptor, indicating that the interaction of this residue with accessory proteins is critical for transcriptional activation. Finally, the occurrence of the L454V mutation in resistance to thyroid hormone, together with impaired negative regulation of the thyroid-stimulating hormone alpha promoter by this mutant, suggests that the amphipathic alpha-helix also mediates hormone-dependent transcriptional inhibition, perhaps via interaction with these or other accessory factors.
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| 2. |
- Delling, Lotta, et al.
(författare)
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Feasibility of bariatric surgery as a strategy for secondary prevention in cardiovascular disease: a report from the Swedish obese subjects trial.
- 2010
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Ingår i: Journal of obesity (Online). - : Hindawi Limited. - 2090-0716 .- 2090-0708. ; 2010
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Forskningsöversikt (refereegranskat)abstract
- Aims. Evaluation of bariatric surgery as secondary prevention in obese patients with ischemic heart disease (IHD). Methods. Analysis of data from 4047 subjects in the Swedish Obese Subjects (SOSs) study. Thirty-five patients with IHD are treated with bariatric surgery (n = 21) or conventional treatment (n = 14). Mean follow-up is 10.8 years. Results. Bariatric surgery resulted in sustained weight loss during the study period. After 2 years, the surgery group displayed significant reductions in cardiovascular risk factors, relief from cardiorespiratory symptoms, increments in physical activity, and improved quality of life. After 10 years, recovery from hypertension, diabetes, physical inactivity, and depression was still more common in the surgery group. There were no signs of increased cardiovascular morbidity or mortality in the surgery group. Conclusion. Bariatric surgery appears to be a safe and feasible treatment to achieve long-term weight loss and improvement in cardiovascular risk factors, symptoms, and quality of life in obese subjects with IHD.
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| 3. |
- Einarsson, Snorri, 1973, et al.
(författare)
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Weight reduction intervention for obese infertile women prior to IVF: a randomized controlled trial.
- 2017
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Ingår i: Human reproduction (Oxford, England). - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 32:8, s. 1621-1630
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Tidskriftsartikel (refereegranskat)abstract
- Does an intensive weight reduction programme prior to IVF increase live birth rates for infertile obese women?An intensive weight reduction programme resulted in a large weight loss but did not substantially affect live birth rates in obese women scheduled for IVF.Among obese women, fertility and obstetric outcomes are influenced negatively with increased risk of miscarriage and a higher risk of maternal and neonatal complications. A recent large randomized controlled trial found no effect of lifestyle intervention on live birth in infertile obese women.A prospective, multicentre, randomized controlled trial was performed between 2010 and 2016 in the Nordic countries. In total, 962 women were assessed for eligibility and 317 women were randomized. Computerized randomization with concealed allocation was performed in the proportions 1:1 to one of two groups: weight reduction intervention followed by IVF-treatment or IVF-treatment only. One cycle per patient was included.Nine infertility clinics in Sweden, Denmark and Iceland participated. Women under 38 years of age planning IVF, and having a BMI ≥30 and <35 kg/m2 were randomized to two groups: an intervention group (160 patients) with weight reduction before IVF, starting with 12 weeks of a low calorie liquid formula diet (LCD) of 880 kcal/day and thereafter weight stabilization for 2-5 weeks, or a control group (157 patients) with IVF only.In the full analysis set (FAS), the live birth rate was 29.6% (45/152) in the weight reduction and IVF group and 27.5% (42/153) in the IVF only group. The difference was not statistically significant (difference 2.2%, 95% CI: 12.9 to -8.6, P = 0.77). The mean weight change was -9.44 (6.57) kg in the weight reduction and IVF group as compared to +1.19 (1.95) kg in the IVF only group, being highly significant (P < 0.0001). Significantly more live births were achieved through spontaneous pregnancies in the weight reduction and IVF group, 10.5% (16) as compared to the IVF only group 2.6% (4) (P = 0.009). Miscarriage rates and gonadotropin dose used for IVF stimulation did not differ between groups. Two subgroup analyses were performed. The first compared women with PCOS in the two randomized groups, and the second compared women in the weight reduction group reaching BMI ≤ 25 kg/m2 or reaching a weight loss of at least five BMI units to the IVF only group. No statistical differences in live birth rates between the groups in either subgroup analysis were found.The study was not powered to detect a small increase in live births due to weight reduction and was not blinded for the patients or physician. Further, the intervention group had a longer time to achieve a spontaneous pregnancy, but were therefore slightly older than the control group at IVF. The study only included women with a BMI lower than 35 kg/m2.The study suggests that weight loss for obese women (BMI: 30-34.9 kg/m2) may not rectify the outcome in IVF cycles, although a significant higher number of spontaneous conceptions occurred in the weight loss group. Also, the study suggests that intensive weight reduction with LCD treatment does not negatively affects the results.The study was funded by Sahlgrenska University Hospital (ALFGBG-70 940), Merck AB, Solna, Sweden (an affiliate of Merck KGaA, Darmstadt, Germany), Impolin AB, Hjalmar Svensson Foundation and Jane and Dan Olsson Foundation. Dr Thurin-Kjellberg reports grants from Merck, non-financial support from Impolin AB, during the conduct of the study, and personal fees from Merck outside the submitted work. Dr Friberg reports personal fees from Ferring, Merck, MSD, Finox and personal fees from Studentlitteratur, outside the submitted work. Dr Englund reports personal fees from Ferring, and non-financial support from Merck, outside the submitted work. Dr Bergh reports and has been reimbursed for: writing a newsletter twice a year (Ferring), lectures (Ferring, MSD, Merck), and Nordic working group meetings (Finox). Dr Karlström reports lectures (Ferring, Finox, Merck, MSD) and Nordic working group meetings (Ferring). Ms Kluge, Dr Einarsson, Dr Pinborg, Dr Klajnbard, Dr Stenlöf, Dr Larsson, Dr Loft and Dr Wistrand have nothing to disclose.ClinicalTrials.gov number, NCT01566929.23-03-2012.05-10-2010.
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| 4. |
- Elias, Erik, 1979, et al.
(författare)
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Central nervous system lipocalin-type prostaglandin D2-synthase is correlated with orexigenic neuropeptides, visceral adiposity and markers of the hypothalamic-pituitary-adrenal axis in obese humans.
- 2011
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Ingår i: Journal of neuroendocrinology. - : Wiley. - 1365-2826 .- 0953-8194. ; 23:6, s. 501-7
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Tidskriftsartikel (refereegranskat)abstract
- Lipocalin-type prostaglandin D2-synthase (L-PGDS) is the main producer of prostaglandin D2 (PGD2) in the central nervous system (CNS). Animal data suggest effects of central nervous L-PGDS in the regulation of food intake and obesity. No human data are available. We hypothesised that a role for CNS L-PGDS in metabolic function in humans would be reflected by correlations with known orexigenic neuropeptides. Cerebrospinal fluid (CSF) and serum samples were retrieved from 26 subjects in a weight loss study, comprising a 3-week dietary lead-in followed by 12-weeks of leptin or placebo treatment. At baseline, CSF L-PGDS was positively correlated with neuropeptide Y (NPY) (ρ=0.695, P<0.001, n=26) and galanin (ρ=0.651, P<0.001) as well as visceral adipose tissue (ρ=0.415, P=0.035). Furthermore, CSF L-PGDS was inversely correlated with CSF leptin (ρ=-0.529, P=0.005) and tended to correlate inversely with s.c. adipose tissue (ρ=-0.346, P=0.084). As reported earlier, leptin treatment had no effect on weight loss and did not affect CSF L-PGDS or NPY levels compared to placebo. After weight loss, the change of CSF L-PGDS was significantly correlated with the change of CSF NPY levels (ρ=0.604, P=0.004, n=21). Because of the correlation between baseline CSF L-PGDS levels and visceral adipose tissue, we examined associations with hypothalamic-pituitary-adrenal (HPA) axis components. Baseline CSF L-PGDS was correlated with corticotrophin-releasing hormone (ρ=0.764, P<0.001) and β-endorphin (ρ=0.491, P<0.001). By contrast, serum L-PGDS was not correlated with any of the measured variables either at baseline or after treatment. In summary, CSF L-PGDS was correlated with orexigenic neuropeptides, visceral fat distribution and central HPA axis mediators. The importance of these findings is unclear but could suggest a role for CSF L-PGDS in the regulation of visceral obesity by interaction with the neuroendocrine circuits regulating appetite and fat distribution. Further interventional studies will be needed to characterise these interactions in more detail.
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| 5. |
- Eskandari, Davoud, et al.
(författare)
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Zonisamide reduces obstructive sleep apnoea: a randomised placebo-controlled study
- 2014
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 44:1, s. 140-149
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Tidskriftsartikel (refereegranskat)abstract
- Carbonic anhydrase inhibition reduces apnoeic events in sleep disordered breathing. Zonisamide inhibits carbonic anhydrase, and induces weight loss in obese patients. This study explored the relative influence of these two properties, which may both alleviate obstructive sleep apnoea (OSA). Continuous positive airway pressure (CPAP) was used as a standard care comparator. 47 patients with moderate-to-severe OSA and a body mass index of 27-35 kg.m(-2) were randomised to receive either zonisamide, placebo or CPAP for 4 weeks. The open extension phase (20 weeks) compared CPAP and zonisamide. Polysomnography, biochemistry and symptoms were evaluated. At 4 weeks, zonisamide reduced apnoea/hypopnoea index (AHI) by a mean +/- SD 33 +/- 39% and oxygen desaturation index by 28 +/- 31% (p=0.02 and 0.014, respectively; placebo adjusted). The mean compliance adjusted reduction of AHI after zonisamide and CPAP was 13 and 61%, respectively, (p=0.001) at 24 weeks. Body weight was marginally changed at 4 weeks, but reduced after zonisamide and increased after CPAP at 24 weeks (-2.7 +/- 3.0 kg versus 2.3 +/- 2.0 kg, p<0.001). Zonisamide decreased bicarbonate at 4 and 24 weeks. Side-effects were more common after zonisamide. Zonisamide reduced OSA independent of body weight potentially by mechanisms related to carbonic anhydrase inhibition. The effect was less pronounced than that obtained by CPAP.
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| 6. |
- Grunstein, R R, et al.
(författare)
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Impact of obstructive sleep apnea and sleepiness on metabolic and cardiovascular risk factors in the Swedish Obese Subjects (SOS) Study.
- 1995
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Ingår i: International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. - 0307-0565. ; 19:6, s. 410-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine if obstructive sleep apnea (OSA) is independently associated with cardiovascular risk factors and health status in subjects with severe obesity. DESIGN: Cross-sectional analysis of epidemiological data. SUBJECTS: 3034 participants in the Swedish Obese Subjects (SOS) Cohort. Two sub-groups with a high and low likelihood for OSA based on questionnaire data were analysed in detail. MEASUREMENTS: General health questionnaires, anthropometric data including CT calibrated values for body fat distribution and lean body mass, blood pressure, fasting insulin, triglycerides, cholesterol, uric acid, glucose. RESULTS: Self-reported loud snoring and observed breathing pauses (high likelihood of OSA) was associated with increased frequency of WHO Grade 4 dyspnea, admissions to hospital with chest pain, myocardial infarction, blood pressure, fasting insulin, fasting triglyceride (women only), uric acid (women only) after adjustment for body fat distribution and other potential confounders. CONCLUSION: OSA may be another medical disorder which contributes to morbidity in severe obesity and is associated with some of the components of the metabolic syndrome observed in the centrally obese.
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| 7. |
- Grunstein, R R, et al.
(författare)
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Impact of self-reported sleep-breathing disturbances on psychosocial performance in the Swedish Obese Subjects (SOS) Study.
- 1995
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Ingår i: Sleep. - 0161-8105. ; 18:8, s. 635-43
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Tidskriftsartikel (refereegranskat)abstract
- Patients with severe obesity commonly have obstructive sleep apnea (OSA). In order to determine the impact of OSA on psychosocial morbidity in severe obesity, subjects enrolled in the Swedish Obese Subjects (SOS) Study were classified into two subgroups based on questionnaire data: one group with a high likelihood and one with a low likelihood of OSA. These groups were contrasted and multivariable analysis was used to examine whether OSA had independent effects on divorce rate, sick leave, work performance, income and self-estimated general health after adjustment for obesity, fat distribution, alcohol, smoking, medications and coexisting medical conditions. A high likelihood of OSA was identified in 338 men and 155 women, compared with 216 men and 481 women who had a low likelihood of OSA. Men with OSA were identical in age to men without OSA and had slightly higher levels of visceral fat (p = 0.01), but were similar in most psychosocial variables except self-perceived general health. Women with OSA were identical in age and visceral fat mass to women without OSA, but were characterized by a higher rate of impaired work performance, sick leave and divorce. When frequent sleepiness was used as an additional discriminator between OSA and non-OSA groups, marked differences in psychosocial morbidity were observed. Multivariable analysis revealed either OSA or frequent sleepiness or both to be independent predictors of amount of sick leave, worse self-rated general health, impaired work performance and divorce rate. Therefore OSA, measured by self report, is an important independent predictor of psychosocial morbidity in subjects with severe obesity.
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| 8. |
- Grunstein, Ronald R, et al.
(författare)
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Two year reduction in sleep apnea symptoms and associated diabetes incidence after weight loss in severe obesity.
- 2007
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Ingår i: Sleep. - 0161-8105. ; 30:6, s. 703-10
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Tidskriftsartikel (refereegranskat)abstract
- STUDY OBJECTIVES: To evaluate the effect of bariatric surgery on sleep apnea symptoms and obesity-associated morbidity in patients with severe obesity. DESIGN: Prospective study. SETTING: University hospitals and community centers in Sweden. Intervention: We investigated the influence of weight loss surgery (n=1729) on sleep apnea symptoms and obesity-related morbidity using a conservatively treated group (n=1748) as a control. MEASUREMENTS AND RESULTS: Baseline BMI in surgical group (42.2+/-4.4 kg/m(2)) and control group (40.1+/-4.6 kg/m(2)) changed -9.7+/-5 kg/m(2) and 0+/-3 kg/m(2), respectively, at 2-year follow-up. In the surgery group, there was a marked improvement in all obstructive sleep apnea (OSA) symptoms compared with the control group (P <0.001). Persistence of snoring (21.6 vs 65.5%, adjusted OR 0.14, 95% CI 0.10-0.19) and apnea (27.9 vs 71.3%, adjusted OR 0.16, 95% I 0.10-0.23) were much less in the surgery group compared with controls. Compared with subjects with no observed apnea at follow-up (n=2453), subjects who continued to have or developed observed apnea (n=404) had a higher incidence of diabetes (adjusted OR 2.03, 95% CI 1.19-3.47) and hypertriglyceridemia (adjusted OR 1.86, 95% CI 1.07-3.25) but not hypertension (adjusted OR 1.09, 95% CI 0.65-1.83) or hypercholesterolemia (adjusted OR 0.91, 95% CI 0.53-1.58). CONCLUSION: Bariatric surgery results in a marked improvement in sleep apnea symptoms at 2 years. Despite adjustment for weight change and baseline central obesity, subjects reporting loss of OSA symptoms had a lower 2-year incidence of diabetes and hypertriglyceridemia. Improvement in OSA in patients losing weight may provide health benefits in addition to weight loss alone.
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| 9. |
- Gummesson, Anders, 1973, et al.
(författare)
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Intestinal Permeability Is Associated With Visceral Adiposity in Healthy Women.
- 2011
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Ingår i: Obesity (Silver Spring, Md.). - : Wiley. - 1930-7381.
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Tidskriftsartikel (refereegranskat)abstract
- Increased visceral fat, as opposed to subcutaneous/gluteal, most strongly relates to key metabolic dysfunctions including insulin resistance, hepatic steatosis, and inflammation. Mesenteric fat hypertrophy in patients with Crohn's disease and in experimental rodent models of gut inflammation suggest that impaired gut barrier function with increased leakage of gut-derived antigens may drive visceral lipid deposition. The aim of this study was to determine whether increased intestinal permeability is associated with visceral adiposity in healthy humans. Normal to overweight female subjects were recruited from a population-based cohort. Intestinal permeability was assessed using the ratio of urinary excretion of orally ingested sucralose to mannitol (S/M). In study 1 (n = 67), we found a positive correlation between waist circumference and S/M excretion within a time frame of urine collection consistent with permeability of the lower gastrointestinal tract (6-9 hours post-ingestion; P = 0.022). These results were followed up in study 2 (n = 55) in which we used computed tomography and dual energy X-ray absorptiometry to measure visceral and subcutaneous fat areas of the abdomen, liver fat content, and total body fat of the same women. The S/M ratio from the 6-12 h urine sample correlated with visceral fat area (P = 0.0003) and liver fat content (P = 0.004), but not with subcutaneous or total body fat. This novel finding of an association between intestinal permeability and visceral adiposity and liver fat content in healthy humans suggests that impaired gut barrier function should be further explored as a possible mediator of excess visceral fat accumulation and metabolic dysfunction.
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| 10. |
- Hedner, Jan A, 1953, et al.
(författare)
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A Randomized Controlled Clinical Trial Exploring Safety and Tolerability of Sulthiame in Sleep Apnea
- 2022
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X. ; 205:12, s. 1461-1469
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Current therapies for obstructive sleep apnea (OSA) are limited by insufficient efficacy, compliance, or tolerability. An effective pharmacological treatment for OSA is warranted. Carbonic anhydrase inhibition has been shown to ameliorate OSA. Objectives: To explore safety and tolerability of the carbonic anhydrase inhibitor sulthiame (STM) in OSA. Methods: A 4-week double-blind, randomized, placebo-controlled dose-guiding trial was conducted in patients with moderate and/or severe OSA not tolerating positive airway pressure treatment. Measurements and Main Results: Intermittent paresthesia was reported by 79%, 67%, and 18% of patients receiving 400 mg STM (n = 34), 200 mg STM (n =12), and placebo (n = 22), respectively. Dyspnea was reported after 400 mg STM (18%). Six patients in the higher dose group withdrew because of adverse events. There were no serious adverse events. STM reduced the apnea-hypopnea index from 55.2 to 33.0 events/h (-41.0%) in the 400-mg group and from 61.1 to 40.6 events/h (-32.1%) after 200 mg (P < 0.001 for both). Corresponding placebo values were 53.9 and 50.9 events/h (-5.4%). The apnea-hypopnea index reduction threshold of >= 50% was reached in 40% of patients after 400 mg, 25% after 200 mg, and 5% after placebo. Mean overnight oxygen saturation improved by 1.1% after 400 and 200 mg (P < 0.001 and P = 0.034, respectively). Patient-related outcomes were unchanged. Conclusions: STM showed a satisfactory safety profile in moderate and/or severe OSA. STM reduced OSA, on average, by more than 20 events/h, one of the strongest reductions reported in a drug trial in OSA. Larger scale clinical studies of STM in OSA are justified.
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| 11. |
- Hoff, Erik, et al.
(författare)
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Carbonic anhydrase, obstructive sleep apnea and hypertension: Effects of intervention
- 2020
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Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 29:2
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Tidskriftsartikel (refereegranskat)abstract
- Whole blood carbonic anhydrase activity (CAa) is increased in patients with obstructive sleep apnea (OSA). Our study investigated the influence of positive airway pressure (PAP) or CA inhibitor acetazolamide (ACT) therapy on CAa, OSA and blood pressure. Thirty‐three OSA patients (21 hypertensive, body mass index (BMI) 37 ± 7 kg/m2 and apnea–hypopnea index (AHI) of 47 ± 31 events/hr) were followed‐up after PAP treatment (compliance, 4.7 ± 1.5 hr/day; duration, median 6 [IQR 6,6] months) (Cohort A). A second OSA Cohort (B) contained nine hypertensive patients (BMI, 29 ± 4 kg/m2; AHI, 39 ± 20 events/hr) with 2‐week treatment of ACT, PAP or ACT + PAP in an open crossover study. CAa was assessed at baseline and at the end of each treatment period. In Cohort A, baseline CAa was higher in hypertensive, compared with normotensive, patients (1,033 ± 204 versus 861 ± 201 units, p = .028). PAP treatment reduced systolic/diastolic blood pressure but not CAa (−9 ± 11/−5 ± 7 mmHg and −20 ± 289 units, p < .001, <.001 and .70). In Cohort B, blood pressure was reduced in both ACT‐treated groups (−10 ± 10/−5 ± 7 mmHg, p = .043 and .019; and −5 ± 5/−13 ± 13 mmHg, p < .001 and .009). AHI was reduced in both groups: ACT only, −17 ± 9 events/hr p = .001; and ACT + PAP, −39 ± 19 events/hr, p < .001. PAP did not change CAa (p = .98) but activity tended to decrease after ACT with or without PAP (p = .081 and .056). CAa is elevated in hypertensive OSA patients. Long‐term PAP reduced blood pressure without affecting CAa. ACT reduced blood pressure and CAa. Increased CAa may constitute a physiological characteristic in OSA, contributing to comorbid hypertension.
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| 12. |
- Hoff, Erik, et al.
(författare)
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Modification of Endotypic Traits in OSA by the Carbonic Anhydrase Inhibitor Sulthiame
- 2024
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Ingår i: CHEST. - 0012-3692 .- 1931-3543. ; 165:3, s. 704-715
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The carbonic anhydrase inhibitor sulthiame reduces OSA severity, increases overnight oxygenation, and improves sleep quality. Insights into how sulthiame modulates OSA pathophysiologic features (endotypic traits) adds to our understanding of the breathing disorder itself, as well as the effects of carbonic anhydrases in respiratory regulation. RESEARCH QUESTION: How does sulthiame treatment modify endotypic traits in OSA? STUDY DESIGN AND METHODS: Per -protocol tertiary analysis of a randomized controlled trial with the inclusion criteria as follow:BMI, >= 20 to # 35 kg/m(2) ; age, 18-75 years; apneahypopnea index (AHI) >= 15 events/h; Epworth sleepiness scale score, >= 6; as well as nonacceptance or nontolerance of positive airway pressure treatment. Patients were randomized to receive placebo (n = 22), sulthiame 200 mg (n = 12), or sulthiame 400 mg (n = 24) during 4 weeks of treatment. Polysomnography was applied twice at baseline and follow-up. Endotypic traits were determined from polysomnography tracings (PUPBeta). Sulthiame plasma concentration was analyzed. Differences from baseline to follow-up ( A s) were analyzed with the analysis of covariance or Kruskal-Wallis H test and Pearson ( r ) or Spearman correlations (r(s)). RESULTS: Sulthiame (200 -mg and 400 -mg groups) consistently reduced loop gain (response to a 1-cycle/min disturbance, Delta G(1) ; mean, - 0.16 [95% CI, - 0.18 to - 0.13]; P < .05) in addition to increased ventilation at lowest decile of ventilatory drive (V (min) ; median, + 12 [95% CI, 420]; P < .05) and median ventilation at eupneic ventilatory drive (V- passive ; median, + 4 [95% CI, 0-5]; P < .05). A Delta G(1 )correlated with A AHI percentage (200 mg: r = 0.65; P < .05). V (min )and V- passive correlated with A AHI (all sulthiame: r(s)= - 0.59 and r(s) = - 0.65; P < .05 for all). The reduction of Delta G(1) was seen already in the lower sulthiame concentration range, whereas changes in V (min) peaked in the higher range. INTERPRETATION: The effect of sulthiame in OSA may be explained by a reduction of ventilatory instability (Delta G(1)) as well as upper airway collapsibility (V (min) and V- passive ).
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| 13. |
- Hoff, Erik, et al.
(författare)
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The placebo effect in pharmacological treatment of obstructive sleep apnea, a systematic review and meta-analysis
- 2023
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Ingår i: Sleep Medicine. - : Elsevier BV. - 1389-9457. ; 106, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Objective: New drug treatments are under development in obstructive sleep apnea (OSA). The placebo effect is well recognized in various conditions, but its relevance in OSA is debated. In the current study we determined the influence of a placebo effect in studies of drug therapy in OSA.Methods: A systematic review and meta-analysis (PROSPERO CRD42021229410) with searches in MEDLINE, Scopus, Web of Science and Cochrane CENTRAL from inception to 2021-01-19. Inclusion criteria were (i) RCTs of adults with OSA, (ii) drug intervention with placebo baseline and follow-up sleep study (iii) outcomes: apnea hypopnea index (AHI), mean oxygen saturation (mSaO2), oxygen desatura-tion index (ODI) and/or Epworth Sleepiness Scale (ESS). Risk-of-bias was assessed with Cochrane RoB 2.Results: 7436 articles were identified and 29 studies included (n = 413). Studies were generally small (median n = 14), with 78% men, baseline AHI range 9-74 events/h and treatment duration range 1-120 days. Meta-analyses were conducted for main outcomes. Mean change of the primary outcome, AHI, was-0.84 (95% CI-2.98 to 1.30); mSaO2 and ODI estimations were also non-significant. ESS showed a trend towards a reduction of-1 unit. Subgroup analysis did not show significant differences. Risk-of-bias assessment indicated mostly low risk but studies were small with wide confidence intervals. Conclusions: In this meta-analysis we did not identify systematic placebo effects on the AHI, ODI or mSaO2 while ESS score showed a trend for a small reduction. These results have an impact on the design and interpretation of drug trials in OSA.(c) 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 14. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Growth hormone treatment of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism, and reduces diastolic blood pressure.
- 1997
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X. ; 82:3, s. 727-34
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Tidskriftsartikel (refereegranskat)abstract
- The most central findings in both GH deficiency in adults and the metabolic syndrome are abdominal/visceral obesity and insulin resistance. Abdominal obesity is associated with blunted GH secretion and low serum insulin-like growth factor-I concentrations. GH treatment in GH-deficient adults has demonstrated favorable effects on most of the features of GH deficiency in adults, but it is not known whether GH can improve some of the metabolic aberrations observed in abdominal/visceral obesity. Thirty men, 48-66 yr old, with abdominal/visceral obesity were treated with recombinant human GH (rhGH) in a 9-month randomized, double-blind, placebo-controlled trial. The daily dose of rhGH was 9.5 micrograms/kg. Body fat was assessed from total body potassium, and abdominal sc and visceral adipose tissue was measured using computed tomography. The glucose disposal rate (GDR) was measured during an euglycemic, hyperinsulinemic glucose clamp. In response to the rhGH treatment, total body fat and abdominal sc and visceral adipose tissue decreased by 9.2 +/- 2.4%, 6.1 +/- 3.2%, and 18.1 +/- 7.6%, respectively. After an initial decrease in the GDR at 6 weeks, the GDR increased in the rhGH-treated group as compared with the placebo-treated one (P < 0.05). The mean serum concentrations of total cholesterol (P < 0.01) and triglyceride (P < 0.05) decreased, whereas blood glucose and serum insulin concentrations were unaffected by the rhGH treatment. Furthermore, diastolic blood pressure decreased and systolic blood pressure was unchanged in response to rhGH treatment. This trial has demonstrated that GH can favorably affect some of the multiple perturbations associated with abdominal/visceral obesity. This includes a reduction in abdominal/visceral obesity, an improved insulin sensitivity, and favorable effects on lipoprotein metabolism and diastolic blood pressure.
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| 15. |
- Karason, Kristjan, 1962, et al.
(författare)
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Relief of cardiorespiratory symptoms and increased physical activity after surgically induced weight loss: results from the Swedish Obese Subjects study.
- 2000
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Ingår i: Archives of internal medicine. - 0003-9926. ; 160:12, s. 1797-802
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obese people frequently suffer from shortness of breath and chest discomfort on exertion, and they often have a sedentary lifestyle. In the present study of patients with severe obesity, we investigated the effects of surgically induced weight loss on cardiorespiratory symptoms and leisure-time physical activity. METHODS: The Swedish Obese Subjects study is an ongoing intervention trial of obesity consisting of 1 surgically treated group and 1 matched control group. Information on smoking habits, hypertension, diabetes, and sleep apnea was obtained from 1210 surgical cases and 1099 controls who were observed for 2 years. Patients were also asked about symptoms of breathlessness and chest pain and their levels of leisure-time physical activity. RESULTS: The surgically treated group displayed a mean weight loss of 28 kg (23%) compared with the control group in which the average weight remained unchanged (P<.001). The rates of hypertension, diabetes, and apneas during sleep decreased in surgical cases compared with controls (P<.001), while smoking habits remained largely the same. The surgical group also displayed highly significant improvements in dyspnea and chest pain and increases in physical activity compared with the control group (P<.001). The odds ratio for self-reported breathlessness, chest discomfort, or sedentary behavior after 2 years decreased progressively with the degree of weight loss. Furthermore, patients who recovered from apneas during sleep reduced their odds of having dyspnea and chest discomfort at follow-up, independent of changes in weight. CONCLUSIONS: Surgically induced weight loss in patients with severe obesity is associated with a marked relief in symptoms of dyspnea and chest pain and promotes increased leisure-time physical activity. Sleep-disordered breathing may be involved in the pathophysiology of breathlessness and chest discomfort in obese subjects.
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| 16. |
- Karlsson, C, et al.
(författare)
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Effects of growth hormone treatment on the leptin system and on energy expenditure in abdominally obese men.
- 1998
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 0804-4643. ; 138:4, s. 408-14
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Tidskriftsartikel (refereegranskat)abstract
- The present study has examined the short- and long-term effects of growth hormone (GH) treatment on the leptin system and energy expenditure. Thirty male individuals with abdominal obesity were randomised to GH or placebo treatment in a 9-month, double-blind study. The dose of GH was 9.5 microg/kg, administered subcutaneously every evening. Serum leptin concentrations were measured by a human leptin RIA. Total RNA was isolated from adipose tissue biopsies and leptin mRNA levels were determined by a semi-quantitative reverse transcriptase-PCR assay. Body composition was determined by potassium-40 and the basal metabolic rate (BMR) was measured by a computerised, ventilated, open-hood system. As compared with placebo, an overall decrease in serum leptin concentrations as assessed by the area under the curve (AUC) (P < 0.05) and an increase in BMR (AUC, P < 0.05) were observed during GH treatment. The overall GH-induced changes were due to marked changes in serum leptin concentrations and BMR after 6 weeks of treatment. After 9 months of GH treatment there was a significant reduction in body fat (BF) while serum leptin concentrations and BMR did not differ from baseline values. Leptin mRNA levels did not change over the study period. We speculate that long-term GH treatment induces a new energy balance steady state with decreased BF stores. The effects of GH on the leptin system is suggested to be of importance for the maintenance of a lower BF mass.
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| 17. |
- Kellis, Dimitrios, 1982, et al.
(författare)
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Associations between obstructive sleep apnea and CT-determined abdominal and liver fat content in severe obese subjects
- 2010
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Ingår i: Obesity Reviews (Poster presentations). - 1467-7881. ; 11:Supplement s1
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Konferensbidrag (refereegranskat)abstract
- Introduction: Obstructive Sleep Apnea (OSA) is a common co-morbidity in obese patients. OSA is also frequently associated with various metabolic complications. In this study, we have evaluated the associations between measures of OSA and abdominal and liver fat subjects with untreated OSA. Methods: A total of 470 subjects (73% females) were examined during a screening process at the Obesity unit at the Sahlgrenska University Hospital. OSA was determined by the ApneaLink system and visceral and liver fat content were determined by CT using a two slice technique at the liver and L4-5 level. The included subjects had a mean age of 42.4 years (SD: 13.5 years), mean weight of 116.6 kg (SD: 20.3 kg), and a mean BMI of 40.8 kg/m2 (SD: 5.7 kg/m2). From the ApneaLink examinations the Apnea - Hypopnea Index (AHI), Respiratory Distress Index (RDI), Oxygen Desaturation Index (ODI) and mean oxygen saturation (SO2) was determined. From the CT examinations visceral adipose tissue mass (VAT) and hepatic fat content (HFC) was determined. Results: VAT was strongly correlated to AHI, RDI, ODI, and SO2 (r = 0.397, 0.388, 0.449, and )0.424 respectively, P < 0.001). There was also a correlation between HFC and AHI, RDI, ODI, and SO2 (r = 0.193, 0.198, 0.214, and 0.173 respectively, P < 0.001). Conclusion: The present study demonstrates that untreated OSA in severe obesity is associated to both measures of visceral fat and hepatic fat content. Evaluations of abdominal fat content should be considered in obese subjects with OSA.
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| 18. |
- Lindroos, Anna-Karin, 1958, et al.
(författare)
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Familial predisposition for obesity may modify the predictive value of serum leptin concentrations for long-term weight change in obese women.
- 1998
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Ingår i: The American journal of clinical nutrition. - 0002-9165. ; 67:6, s. 1119-23
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is believed to play a role in regulating food intake and body weight. The aim of this study was to examine the influence of parental history of obesity on the association between baseline serum leptin concentrations and subsequent 4-y weight changes. Changes in food intake were also considered in the analysis. Middle-aged, obese women with no obese parent (n = 25) or at least one obese parent (n = 24) were included in the analysis. At baseline, women with no parental history of obesity and women with a parental history of obesity did not differ in body mass index (in kg/m2: 41.2 and 40.2, respectively) or median leptin concentrations (40.8 and 38.8 microg/L, respectively). Four-year weight changes varied widely in both groups combined (from -30 to 24 kg). Stratified regression analysis, adjusted for age, weight, and height, revealed that high leptin concentrations predicted less weight gain (or more weight loss) in women with no obese parent (beta = -21.2, P = 0.0006) but played no significant role in predicting weight gain in women with at least one obese parent (beta = -3.8, P = 0.41). Adding changes in energy and fat intakes to the model reduced the association between leptin and weight change to nonsignificance in the women with no obese parent, indicating that the effect of leptin could be explained largely by dietary changes. In conclusion, serum leptin concentrations predict long-term weight change in obese women with no history of parental obesity, an association largely mediated by changes in food intake.
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| 19. |
- Lundén, A, et al.
(författare)
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Validation of the Obesity-related Problem Scale version 3
- 2010
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Ingår i: Obesity Reviews (Poster presentations). - 1467-7881. ; 11:Supplement s1
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Konferensbidrag (refereegranskat)abstract
- Introduction: The Obesity-related Problem scale (OP) is a quality of life instrument developed to measure the impact of obesity on psychosocial functioning. Subjects are asked how bothered they are by their obesity in specific social situations. A new version of the instrument (OP V3) has been developed. Eight more items were added. Also, an avoidance scale (AV) was added to each item, measuring avoidance of social activities. Thus, the OP V3 contains both a distress and an avoidance scale. The aim of the present study was to investigate the construct validity of OP V3. Methods: One eighty subjects, BMI 40.7˘ 5.3 kg/m2, completed the OP V3. The construct validity of OP V3 was studied by means of exploratory factor analyses. Internal consistency reliability, floor and ceiling effects, concurrent validity and known group validation were also examined. SF-36 was used to evaluate the concurrent validity. Results: Scale internal consistency reliability was high for both the distress and avoidance scales (Cronbach’s alpha = 0.95 for both). Floor and ceiling effects were small. Exploratory factor analyses confirmed the homogeneity and stability of the construct. Psychometric results were cross-validated and replicated in subgroups by gender, age and BMI. Multitrait-Multimethod analysis showed moderate associations between the OP V3 scales and the SF-36 scales. Correlations ranged from )0.32 to )0.58, P < 0.001. As expected, OP V3 scales were most highly correlated with Social functioning, Mental health and Vitality (r = )0.51 to )0.58, P < 0.001). Conclusions: Results confirm that OP V3 is a psychometrically valid measure of the impacts of obesity on psychosocial functioning.
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| 20. |
- Lönn, Lars, 1956, et al.
(författare)
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Body weight and body composition changes after treatment of hyperthyroidism.
- 1998
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X. ; 83:12, s. 4269-73
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Tidskriftsartikel (refereegranskat)abstract
- Body composition changes in nine adults with hyperthyroidism were determined with dual energy x-ray absorptiometry and computed tomography at diagnosis and after 3 and 12 months of euthyroidism achieved by surgery, antithyroid drugs, or treatment with radioiodine. Mean body weight was 67.6 kg at diagnosis and increased 2.7 kg (P=0.06) and 8.7 kg (P < 0.001) after 3 and 12 months of euthyroidism, respectively. Basal metabolic rate decreased from 2087 Cal/24 h at diagnosis to 1601 Cal/24 h at 12 months (P=0.001), whereas reported energy intake dropped from 3244 to 2436 Cal/24 h (P=0.01). According to dual energy x-ray absorptiometry, body fat was unchanged at 3 months, but increased by 5.3 kg (P < 0.0001) at 12 months. Fat-free mass increased 2.7 kg (P=0.003) at 3 months and 3.5 kg (P < 0.0001) at 12 months. Changes in bone mineral content and density did not reach significance. According to computed tomography, skeletal muscle plus skin areas increased by 11% (trunk) and 18% (thigh) at 3 months and by 17% (trunk) and 25% (thigh) at 12 months. There was no increase in sc adipose tissue (AT) at 3 months, but at 12 months this AT depot increased by 15% (thigh) and 33% (trunk). Intraperitoneal AT showed a borderline significant increase by 28% (P=0.08) at 3 months and by 40% (P=0.015) at 12 months. Areas of visceral organs and bone tissue of femur did not change significantly during the study. It is concluded that during early recovery from hyperthyroidism, priority is given to the replenishment of skeletal muscles and ip AT, whereas sc AT is increased at a later stage.
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| 21. |
- Marshall, N.S., et al.
(författare)
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Changes in sleep duration and changes in weight in obese patients: The Swedish Obese Subjects Study
- 2010
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Ingår i: Sleep and Biological Rhythms. - : Springer Science and Business Media LLC. - 1479-8425 .- 1446-9235. ; 8:1, s. 63-71
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Tidskriftsartikel (refereegranskat)abstract
- Sleep duration has been linked to obesity and/or weight gain in a number of cross-sectional and longitudinal observational studies. The Swedish Obese Subjects Study (SOS) is a non-randomized controlled trial of surgical interventions (surgical group) for weight-loss compared with standard conservative weight loss management (control group). We investigated whether changes in sleep duration were associated with weight loss in severely obese patients. This is a longitudinal treatment study reanalyzed as two 10-year cohorts, surgical (n= 1139) and control (n= 952). Self-reported habitual sleep duration, body weight, total cholesterol, HDL (high density lipoprotein) cholesterol, triglycerides, fasting glucose, and blood pressure were measured at baseline, 2 years, and 10 years. At baseline patients were obese (inclusion: body mass index [BMI]≥34 for men and ≥38 for women) and middle aged (37–60 years). The surgical group had substantially greater weight reduction after 10 years (–19.1 kg) compared with the control group (+1.2 kg). Changes in sleep duration between baseline, 2 years, and 10 years were not associated with body mass or with changes in weight in either cohort. Changes in cardiovascular disease (CVD) risk factors were not associated with changes in sleep duration. Changes in sleep duration over 2 and 10 years were not associated with weight loss in these obese patients. The data from the SOS study offers no support to the hypothesis that sleep-duration modification is associated with obesity reduction in severely obese people.
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| 22. |
- Marshall, N.S., et al.
(författare)
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Self-reported sleep apnoea and mortality in patients from the Swedish Obese Subjects study
- 2011
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 38:6, s. 1349-1354
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Tidskriftsartikel (refereegranskat)abstract
- Sleep apnoea is associated with increased mortality in sleep clinic and community population groups. It is unclear whether a clinical report of sleep apnoea results in additional mortality risk in patients with severe obesity. The Swedish Obese Subjects (SOS) study is a nonrandomised controlled trial of bariatric surgery versus conventional treatment for the treatment of severe obesity and its complications (mean±sd body mass index 41±5 kg·m−2). The presence or absence of sleep apnoea (witnessed pauses in breathing) was determined by self-reporting at baseline in 3,953 patients who were observed for 54,236 person-yrs (mean 13.5 maximum 21.0 yrs). Sleep apnoea was reported by 934 (23.6%) patients at baseline and was a significant univariate predictor of mortality (hazard ratio (95% CI) 1.74 (1.40–2.18)). In a range of multivariate models of mortality risk, controlling for ≤16 other potential confounders and established mortality risk factors, sleep apnoea remained a significant prognostic factor (fully adjusted model 1.29 (1.01–1.65)). Self-reported sleep apnoea is an independent prognostic marker of all-cause mortality in obese patients.
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| 23. |
- Persson, Josefine, 1981, et al.
(författare)
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Long-term QALY-weights among spouses of dependent and independent midlife stroke survivors.
- 2017
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Ingår i: Quality of Life Research. - : Springer Science and Business Media LLC. - 0962-9343 .- 1573-2649. ; 26:11, s. 3059-3068
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was to investigate whether the dependency of midlife stroke survivors had any long-term impact on their spouses' QALY-weights. METHOD: Data on stroke survivors, controls, and spouses were collected from the 7-year follow-up of the Sahlgrenska Academy Study on Ischemic Stroke. Health-related quality of life was assessed by the SF-36, and the preference-based health state values were assessed with the SF-6D. Spouses of dependent and independent stroke survivors were categorized according to their scores on the modified Rankin Scale. An ordinary least squares regression analysis was used to evaluate whether the dependency of the stroke survivors had any impact on the spouses' QALY-weights. RESULT: Cohabitant dyads of 247 stroke survivors aged <70 at stroke onset and 245 dyads of controls were included in the study. Spouses of dependent stroke survivors (n = 50) reported a significant lower mean QALY-weight of 0.69 in comparison to spouses of independent stroke survivors (n = 197) and spouses of controls, (n = 245) who both reported a mean QALY-weight of 0.77. The results from the regression analysis showed that higher age of the spouse and dependency of the stroke survivor had a negative association with the spouses' QALY-weights. CONCLUSION: The QALY-weights for spouses of dependent midlife stroke survivors were significantly reduced compared to spouses of independent midlife stroke survivors. This indicates that the inclusion of spouses' QALYs in evaluations of early treatment and rehabilitation efforts to reduce stroke patients' dependency would capture more of the total effect in dyads of stroke survivors.
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| 24. |
- Ryan, Donna H, et al.
(författare)
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Nonsurgical weight loss for extreme obesity in primary care settings: results of the Louisiana Obese Subjects Study.
- 2010
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Ingår i: Archives of internal medicine. - : American Medical Association (AMA). - 1538-3679 .- 0003-9926. ; 170:2, s. 146-54
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Effective primary care practice (PCP) treatments are needed for extreme obesity. The Louisiana Obese Subjects Study (LOSS) tested whether, with brief training, PCPs could effectively implement weight loss for individuals with a body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 40 to 60. METHODS: The LOSS, a 2-year (July 5, 2005, through January 30, 2008) randomized, controlled, "pragmatic clinical trial" trained 7 PCPs and 1 research clinic in obesity management. Primary outcome measure was year-2 percentage change from baseline weight. Volunteers (597) were screened and randomized to intensive medical intervention (IMI) (n = 200) or usual care condition (UCC) (n = 190). The UCC group had instruction in an Internet weight management program. The IMI group recommendations included a 900-kcal liquid diet for 12 weeks or less, group behavioral counseling, structured diet, and choice of pharmacotherapy (sibutramine hydrochloride, orlistat, or diethylpropion hydrochloride) during months 3 to 7 and continued use of medications and maintenance strategies for months 8 to 24. RESULTS: The mean age of participants was 47 years; 83% were women, and 75% were white. Retention rates were 51% for the IMI group and 46% for the UCC group (P = .30). After 2 years, the results were as follows: (1) among 390 randomized participants, 31% in the IMI group achieved a 5% or more weight loss and 7% achieved a 20% weight loss or more, compared with 9% and 1% of those in the UCC group. (2) The mean +/- SEM baseline observation carried forward analysis showed a weight loss of -4.9% +/- 0.8% in IMI and -0.2 +/- 0.3% in UCC. (3) Last observation carried forward analysis showed a weight loss of -8.3% +/- 0.79% for IMI, whereas UCC was -0.0% +/- 0.4%. (4) A total of 101 IMI completers lost -9.7% +/- 1.3% (-12.7 +/- 1.7 kg), whereas 89 UCC completers lost -0.4% +/- 0.7% (-0.5 +/- 0.9 kg); (P < .001 for all group differences). Many metabolic parameters improved. CONCLUSION: Primary care practices can initiate effective medical management for extreme obesity; future efforts must target improving retention and weight loss maintenance. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00115063.
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| 25. |
- Sjöström, Lars, et al.
(författare)
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Effects of bariatric surgery on cancer incidence in obese patients in Sweden (Swedish Obese Subjects Study): a prospective, controlled intervention trial.
- 2009
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Ingår i: The lancet oncology. - 1474-5488. ; 10:7, s. 653-62
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obesity is a risk factor for cancer. Intentional weight loss in the obese might protect against malignancy, but evidence is limited. To our knowledge, the Swedish Obese Subjects (SOS) study is the first intervention trial in the obese population to provide prospective, controlled cancer-incidence data. METHODS: The SOS study started in 1987 and involved 2010 obese patients (body-mass index [BMI] >or=34 kg/m(2) in men, and >or=38 kg/m(2) in women) who underwent bariatric surgery and 2037 contemporaneously matched obese controls, who received conventional treatment. While the main endpoint of SOS was overall mortality, the main outcome of this exploratory report was cancer incidence until Dec 31, 2005. Cancer follow-up rate was 99.9% and the median follow-up time was 10.9 years (range 0-18.1 years). FINDINGS: Bariatric surgery resulted in a sustained mean weight reduction of 19.9 kg (SD 15.6 kg) over 10 years, whereas the mean weight change in controls was a gain of 1.3 kg (SD 13.7 kg). The number of first-time cancers after inclusion was lower in the surgery group (n=117) than in the control group (n=169; HR 0.67, 95% CI 0.53-0.85, p=0.0009). The sex-treatment interaction p value was 0.054. In women, the number of first-time cancers after inclusion was lower in the surgery group (n=79) than in the control group (n=130; HR 0.58, 0.44-0.77; p=0.0001), whereas there was no effect of surgery in men (38 in the surgery group vs 39 in the control group; HR 0.97, 0.62-1.52; p=0.90). Similar results were obtained after exclusion of all cancer cases during the first 3 years of the intervention. INTERPRETATION: Bariatric surgery was associated with reduced cancer incidence in obese women but not in obese men. FUNDING: Swedish Research Council, Swedish Foundation for Strategic Research, Swedish Federal Government under the LUA/ALF agreement, Hoffmann La Roche, Cederoths, AstraZeneca, Sanofi-Aventis, Ethicon Endosurgery.
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| 26. |
- Sjöström, Lars, et al.
(författare)
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Effects of bariatric surgery on mortality in Swedish obese subjects.
- 2007
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Ingår i: The New England journal of medicine. - 1533-4406. ; 357:8, s. 741-52
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obesity is associated with increased mortality. Weight loss improves cardiovascular risk factors, but no prospective interventional studies have reported whether weight loss decreases overall mortality. In fact, many observational studies suggest that weight reduction is associated with increased mortality. METHODS: The prospective, controlled Swedish Obese Subjects study involved 4047 obese subjects. Of these subjects, 2010 underwent bariatric surgery (surgery group) and 2037 received conventional treatment (matched control group). We report on overall mortality during an average of 10.9 years of follow-up. At the time of the analysis (November 1, 2005), vital status was known for all but three subjects (follow-up rate, 99.9%). RESULTS: The average weight change in control subjects was less than +/-2% during the period of up to 15 years during which weights were recorded. Maximum weight losses in the surgical subgroups were observed after 1 to 2 years: gastric bypass, 32%; vertical-banded gastroplasty, 25%; and banding, 20%. After 10 years, the weight losses from baseline were stabilized at 25%, 16%, and 14%, respectively. There were 129 deaths in the control group and 101 deaths in the surgery group. The unadjusted overall hazard ratio was 0.76 in the surgery group (P=0.04), as compared with the control group, and the hazard ratio adjusted for sex, age, and risk factors was 0.71 (P=0.01). The most common causes of death were myocardial infarction (control group, 25 subjects; surgery group, 13 subjects) and cancer (control group, 47; surgery group, 29). CONCLUSIONS: Bariatric surgery for severe obesity is associated with long-term weight loss and decreased overall mortality.
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| 27. |
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| 28. |
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| 29. |
- Smith, SR, et al.
(författare)
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The effect of orlistat 60 mg on changes in body composition over a 24 week treatment: a randomized, placebo-controlled, multicenter study
- 2010
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Ingår i: Obesity Reviews (Poster presentations). - 1467-7881. ; 11:Supplement s1
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Konferensbidrag (refereegranskat)abstract
- Introduction: A paucity of data exists on the effects of 60 mg orlistat on changes in body composition, particularly visceral adipose tissue (VAT). Methods: Overweight and obese adults (BMI 25–34.9) with a waist circumference >88 cm (women) or >102 cm (men) were randomized to either orlistat 60 mg (n = 61) or placebo (n = 62) tid for 6 months to examine changes in body composition. Subjects were encouraged to maintain a hypocaloric (-500 kcals/day), low fat (30% calories from fat) diet and were encouraged to exercise. Change from baseline for VAT (kg) by CT was examined at 12 and 24 weeks by ANCOVA. Change from baseline in total fat mass (FM) by EchoMRI, body weight, and waist circumference were examined across multiple time points beginning at week 2 using repeated measure analysis. Results: Mean changes from baseline for all variables were significant in both groups. VAT reduction was greater with orlistat compared to placebo at 12 (LS mean ± SE; )0.50 ± 0.06 vs. )0.32 ± 0.06, P < 0.05) and 24 weeks ()0.62 ± 0.08 vs. )0.32 ± 0.08 P < 0.01). A significantly greater reduction was observed over the 24 weeks in the orlistat group for FM and body weight, as compared to placebo (Group effect P < 0.05), but not waist circumference. Conclusion: Orlistat 60 mg provided significantly greater reductions in weight, FM and VAT across 24 weeks, compared to placebo. The reductions in VAT were relatively stable from 12 to 24 weeks in placebo subjects, whereas VAT reduction in orlistat-treated subjects continued over the 24 week duration.
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| 30. |
- Stenlöf, Kaj, 1965, et al.
(författare)
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Diurnal variations in twenty-four-hour energy expenditure during growth hormone treatment of adults with pituitary deficiency.
- 1997
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 82:4, s. 1255-60
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Tidskriftsartikel (refereegranskat)abstract
- The effects of growth hormone (GH) treatment on 24-h energy expenditure (EE) were studied in a open trial over a period of 4 weeks. Five subjects, four men and one woman, with a history of complete GH deficiency were included. All the subjects were examined on 2 consecutive days on baseline and, thereafter, at six occasions during a period of 1 month (days 1, 2, 5, 8, 15, and 30). The dose of GH was 0.25 U/kg.week, administered sc once a day in the evening. EE was determined in a chamber for indirect calorimetry. Body composition was determined with dual-energy x-ray absorptiometry and computed tomography using a four-scan technique. Blood samples were examined using well-established RIAs. During the first 2 weeks, 24-h EE increased by 6 +/- 3% (range 1-8%) from 40.9 +/- 4.8 to 42.9 +/- 4.8 kcal/24 h.kg (P < 0.05), sleeping metabolic rate by 14 +/- 3% (range 10-18%) from 28.4 +/- 1.9 to 32.9 +/- 2.2 kcal/24h.kg (P < 0.001), and basal metabolic rate by 11 +/- 7% (range 0-18%) from 29.6 +/- 2.4 to 33.3 +/- 2.6 kcal/24h.kg (P < 0.05). No change was found in daytime EE. The increase in EE covaried with changes in insulin-like growth factor 1, the free T3/free T4 ratio, insulin-like growth factor-binding protein-3, and the aminoterminal procollagen III peptide but not with changes in body composition. It is suggested that the stimulating effect of GH on EE occurs gradually during a 2-week period and is only detectable during night and morning hours, when significant levels of GH occur.
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| 31. |
- Stenlöf, Kaj, 1965, et al.
(författare)
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Effects of recombinant human growth hormone on basal metabolic rate in adults with pituitary deficiency.
- 1995
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Ingår i: Metabolism: clinical and experimental. - 0026-0495. ; 44:1, s. 67-74
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Tidskriftsartikel (refereegranskat)abstract
- The effect of recombinant human growth hormone (rhGH) on basal metabolic rate (BMR) was studied in a placebo-controlled, double-blind, crossover trial. Ten patients with a history of complete pituitary insufficiency were randomized for 26 weeks in each period. Three patients were excluded due to withdrawal, fever, and claustrophobia, respectively. All patients had received adrenal, thyroid, and gonadal substitution therapy for at least 1 year before the study. The dose of rhGH was 0.25 to 0.5 U/kg/wk, administered subcutaneously once a day in the evening. BMR was determined by indirect calorimetry in a computerized ventilated open-hood system. Body composition was examined using four different methods--computed tomography (CT), tritium dilution, 40K determinations, and total body nitrogen (TBN) measured with neutron activation. The body composition data have previously been reported. Fat-free mass (FFM) increased and body fat (BF) decreased during the first 6 weeks of rhGH treatment, but no further changes in body composition occurred between 6 and 26 weeks. Baseline BMRs in GH-deficient (GHD) patients were in the lower part of the reference range, but BMR and the ratio between BMR and FFM (BMR/FFM) were not significantly lower than in a carefully selected control group. BMR increased between 0 and 6 weeks (mean +/- SD: from 6.68 +/- 1.55 to 7.75 +/- 1.35 MJ/24 h, P < .001) and then remained unchanged between 6 and 26 weeks. The increase in BMR was closely related to the increase in FFM (r = .91, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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| 32. |
- Stenlöf, Kaj, 1965, et al.
(författare)
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Effects of the microsomal triglyceride transfer protein (MTP) inhibitor JNJ-16269110 on glycemic control and body weight in subjects with type 2 diabetes mellitus (T2DM) on metformin
- 2010
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Ingår i: Obesity Reviews (Poster presentations). - 1467-7881. ; 11:Supplement s1
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Konferensbidrag (refereegranskat)abstract
- Introduction: JNJ-16269110 is a novel enterocyte-targeted MTP inhibitor acting via enterically-mediated hormonal and neural mechanisms being investigated for treatment of obesity. Methods: Three hundred and fifty two subjects with T2DM (BMI 32.8 kg/m2; 54% males) were randomized to placebo, JNJ-16269110 5-mg bid, 10-mg bid or 15-mg bid for 12 weeks in a double-blind multicenter clinical trial to assess safety and efficacy of this agent. The primary efficacy endpoint was change from baseline to Week 12 in HbA1c (ITT-mixed-model). Secondary endpoints included changes in fasting plasma glucose (FPG), body weight (BW), and plasma lipids. Results: Gastrointestinal symptoms were the most common reason for early discontinuation in the JNJ-16269110 arms (2%, 12%, 9% of subjects in 5-mg, 10-mg, 15-mg bid groups, respectively, vs. 1% in placebo group). Conclusion: Compared to placebo, JNJ-16269110 10-mg and 15-mg bid improved glycemic control and reduced BW. The most common side effects were related to the astrointestinal system. Conflict of interest: K. Stenlof received funding from Johnson and Johnson as principal investigator and consultant. E. Wajs, F. Vercruysse, D. Ways, S. Ouwerkerk-Mahadevan, J. Penson, and L. Van Nueten are employees and shareholders of Johnson and Johnson. Funding: The study was funded by Johnson & Johnson Pharmaceutical Research and Development.
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| 33. |
- Stenlöf, Kaj, 1965, et al.
(författare)
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Energy expenditure in obstructive sleep apnea: effects of treatment with continuous positive airway pressure.
- 1996
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Ingår i: The American journal of physiology. - 0002-9513. ; 271:6 Pt 1
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Tidskriftsartikel (refereegranskat)abstract
- We examined 24-h energy expenditure (EE) in a chamber for indirect calorimetry in five male patients with obstructive sleep apnea (OSA) and six snoring control subjects (snorers). The 24-h EE was remeasured in patients with OSA after 3-mo treatment with nasal continuous positive airway pressure (CPAP). Patients with OSA had a greater degree of severe sleep-breathing disturbance than snorers. Patients with OSA had higher 24-h EE [39.2 +/- 3.0 vs. 33.9 +/- 2.7 kcal.24 h-1.kg fat-free mass (FFM)-1, P < 0.05], daytime urinary norepinephrine and vanillylmandelic acid (VMA), and aminoterminal procollagen III peptide (PIIIp) levels, and they tended to have higher sleeping EE (32.4 +/- 4.1 vs. 26.3 +/- 1.9 kcal.24 h-1.kg FFM-1, P < 0.1) than snorers. CPAP treatment normalized sleep architecture and breathing. CPAP treatment also decreased sleep EE (from 32.4 +/- 4.1 to 27.2 +/- 1.4 kcal.24 h-1.kg FFM-1, P < 0.05) and EE variability during sleep (from 1.6 +/- 0.5 to 1.0 +/- 0.5 kcal.24 h-1.kg FFM-1, P < 0.05) and increased the basal metabolic rate-to-sleep EE ratio in all subjects. Serum PIIIp and plasma norepinephrine decreased after CPAP in all patients. We conclude that OSA is associated with an increased sleep EE, which is normalized by treatment with CPAP.
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| 34. |
- Stenlöf, Kaj, 1965, et al.
(författare)
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Interleukin-6 levels in the central nervous system are negatively correlated with fat mass in overweight/obese subjects.
- 2003
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 88:9, s. 4379-83
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Tidskriftsartikel (refereegranskat)abstract
- Recently, we demonstrated that intracerebroventricular injection of IL-6 increases energy expenditure and decreases body fat in rodents. Therefore, IL-6 may play a role in appetite and body weight control in the central nervous system. In the present study we evaluated cerebrospinal fluid (CSF) and serum IL-6 levels in humans in relation to body fat content and to CSF and serum levels of leptin. Thirty-two healthy overweight/obese male subjects with a body mass index range of 29.3-36.0 kg/m(2) were studied. Total and sc body fat were measured by dual energy x-ray absorptiometry and computed tomography, respectively. CSF IL-6 levels were in some individuals higher than serum IL-6 levels and correlated negatively with total body weight, sc and total body fat. In contrast, CSF leptin levels were 30-60 times lower than serum leptin levels and correlated positively with serum leptin, body weight, sc and total body fat. Furthermore, there was a negative correlation between CSF IL-6 and leptin. In conclusion, CSF IL-6 differs in many ways from CSF leptin. CSF IL-6 may be locally produced rather than serum derived, and body fat-regulating regions in the central nervous system may be exposed to insufficient IL-6 levels in more severe obesity.
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| 35. |
- Stenlöf, Kaj, 1965
(författare)
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Recent Advances in the Use of Orlistat in the Treatment of Abdominal Obesity and Associated Cardiometabolic Risk Factors
- 2010
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Ingår i: Journal of Clinical Metabolism & Diabetes. - 2041-8019. ; 1:1, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a serious health concern in several parts of the world. During the last few years, the prevalence of abdominal obesity has attracted specific attention, as abdominal obesity and visceral obesity are associated with several important metabolic disturbances and explain most of the increased risk for cardiovascular disease (CVD) associated with obesity. Thus, in the clinical evaluation of obese patients with an increased risk for CVD, it is important to aim to reduce abdominal fat. Lifestyle interventions, including diet and physical activity, should be first-line treatments; however, pharmaceutical agents might also be considered. Not surprisingly, abdominal and visceral obesity are important targets for drug development. Orlistat is an existing pharmacological agent available for the long-term treatment of obesity. This drug inhibits gastric and pancreatic lipase degradation of triglycerides in the intestine, such that ingested triglycerides cannot be hydrolyzed or absorbed. Orlistat has been investigated in several large studies that demonstrated its efficacy and safety, and is currently available in more than 120 countries, with more than 40 million doses having been distributed worldwide (www.fda.gov/Drugs/, May 2010). The purpose of this report is to provide a short review of the available data regarding the effects of orlistat on abdominal obesity and associated metabolic disturbances.
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| 36. |
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| 37. |
- Stenlöf, Kaj, 1965, et al.
(författare)
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Significant reduction in body fat assessed by echomri in subjects treated with orlistat 60 mg for 6 months compared with placebo: relationships between changes in body composition and body weight
- 2010
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Ingår i: Obesity Reviews (Poster presentations). - 1467-7881. ; 11:Supplement s1
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Konferensbidrag (refereegranskat)abstract
- Introduction: A randomised, double-blind study has demonstrated that orlistat 60 mg is significantly more effective than placebo in reducing visceral fat measured by CT (1). New data from this multicentre study are used to investigate associations between changes in body composition [EchoMRI, total fat mass; body impedance analysis (BIA), % body fat] and body weight. Methods: Adults (BMI 25–34.9 kg/m2) with a waist circumference >88 cm (women) or 102 cm (men) were randomised to receive orlistat 60 mg or placebo, 3x/day for 6 months. A reduced calorie, lower-fat diet was recommended and subjects were encouraged to exercise. Body fat was measured at baseline and weeks 2, 4, 12, and 24. Results: Demographic and baseline characteristics were similar between orlistat 60 mg (n = 62) and placebo (n = 61) groups. Conclusion: Orlistat 60 mg was significantly more effective than placebo in reducing body fat as assessed by EchoMRI and BIA. Change in total fat mass measured by EchoMRI was highly correlated with change in body weight, but the association with weight loss was less marked when measured by BIA (1). Orlistat 60 mg demonstrates a significant reduction in visceral adipose tissue at 24 weeks compared with placebo. Abstract presented at ICAO, Hong Kong, January 2010. Conflict of interest: Investigator, GlaxoSmithKline Consumer Healthcare.
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| 38. |
- Stenlöf, Kaj, 1965, et al.
(författare)
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Thyroid hormones, procollagen III peptide, body composition and basal metabolic rate in euthyroid individuals.
- 1993
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Ingår i: Scandinavian journal of clinical and laboratory investigation. - 0036-5513. ; 53:8, s. 793-803
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Tidskriftsartikel (refereegranskat)abstract
- We examined 103 euthyroid men and women within a wide range of body weights and ages. Fat free mass (FFM) and body fat (BF) were determined with the total body potassium technique, basal metabolic rate (BMR) by indirect calorimetry and serum concentrations of thyroid hormones (free and total T3 and T4) and the aminoterminal propeptide of collagen III (pIIIp) by immunoassays. BMR was positively related to FFM, BF, total T3, the free T3/free T4 ratio and pIIIp, and negatively to free T4 (men) and to the ratios free T4/total T4 and free T3/total T3. pIIIp was as strongly related to BMR as to total T3. It is suggested that pIIIp may serve as an indicator of peripheral energy expenditure. The negative relationship between BMR and free T4 was unexpected and different to the situation in hypo- and hyperthyreosis where BMR and thyroid hormone are positively related. Our hypothesis is that euthyroid subjects with low serum free thyroid hormone concentrations and comparatively high BMR may have high intracellular thyroid hormone concentrations.
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| 39. |
- Stenlöf, Kaj, 1965, et al.
(författare)
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Topiramate in the treatment of obese subjects with drug-naive type 2 diabetes.
- 2007
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Ingår i: Diabetes, obesity & metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 9:3, s. 360-8
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The aim of this study was to examine the efficacy and safety of topiramate as an adjunct to diet and exercise in drug-naive, obese subjects with type 2 diabetes. METHODS: Drug-naive individuals with type 2 diabetes, body mass index (BMI) of > or =27 and <50 kg/m(2) and haemoglobin A(1c) (HbA(1c)) of <10.5% were enrolled into the study. All the individuals participated in a non-pharmacologic weight loss program (Pathways to Change((R)); Johnson & Johnson Healthcare Systems, Piscataway, NJ, USA) throughout the trial. After a 6-week placebo run-in, the subjects were randomized to placebo, topiramate 96 mg/day or topiramate 192 mg/day. Subjects were scheduled for 8-week titration and 52-week maintenance phases. The study was ended early; efficacy data were reported for a predefined modified intent-to-treat (MITT) population (n = 229), with 40 weeks of treatment. All the subjects who provided any safety data were included in the safety population (n = 535). RESULTS: Baseline mean weight was 103.7 kg, BMI 36 kg/m(2) and HbA(1c) 6.7% across all treatment groups. By the end of week 40, the placebo, the topiramate 96 mg/day and topiramate 192 mg/day groups lost 2.5, 6.6 and 9.1% of their baseline body weight respectively (p < 0.001 vs. placebo, MITT population using last observation carried forward). The decrease in HbA(1c) was 0.2, 0.6 and 0.7% respectively (p < 0.001 vs. placebo, MITT). Topiramate significantly reduced blood pressure and urinary albumin excretion; a weight-loss-independent HbA(1c) improving effect of topiramate was demonstrated. Adverse events were predominantly related to central nervous system (CNS). CONCLUSIONS: Topiramate as an add-on treatment to lifestyle improvements produced significant weight loss and improved glucose homeostasis in obese, drug-naive subjects with type 2 diabetes. These treatment advantages should be balanced against the occurrence of adverse events in the CNS.
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| 40. |
- Torgerson, Jarl S, 1960, et al.
(författare)
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A low serum leptin level at baseline and a large early decline in leptin predict a large 1-year weight reduction in energy-restricted obese humans.
- 1999
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 84:11, s. 4197-203
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Tidskriftsartikel (refereegranskat)abstract
- The difficulty in maintaining weight loss during obesity treatment may be caused by a counteracting neuroendocrine response. It has been proposed that leptin could be a regulator of this response. We examined the relations between leptin levels during an initial very low calorie diet, other simultaneous endocrine changes, and the 1-yr weight reduction. Sixty-nine obese (24 men and 45 women) were treated with very low calorie diet for 16 weeks, followed by a hypocaloric diet for 32 weeks. Serum levels of leptin, insulin, cortisol, and thyroid hormones were measured at weeks 0, 8, and 18. The relative weight reductions after 18 and 48 weeks were 20.1% and 14.4% in men and 15.4% and 11.8% in women. Low initial leptin levels and large declines in serum leptin were associated with a large 1-yr weight loss in both genders. Leptin levels (baseline or changes) were not independently associated with the changes in insulin, cortisol, or thyroid hormones. Our results may indicate that leptin by itself could be of minor importance for the neuroendocrine response to severe caloric restriction in humans.
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| 41. |
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| 42. |
- Zelissen, P M J, et al.
(författare)
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Effect of three treatment schedules of recombinant methionyl human leptin on body weight in obese adults: a randomized, placebo-controlled trial.
- 2005
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Ingår i: Diabetes, obesity & metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 7:6, s. 755-61
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The aim of this study was to evaluate the effect on body weight and safety of subcutaneously administered recombinant leptin in obese adults and to evaluate whether the timing of recombinant leptin administration influences efficacy. METHODS: A randomized, double-blind, placebo-controlled, multicentre study was designed, comprising of a 3-week dietary lead-in followed by a 12-week leptin or placebo treatment period. A total of 284 overweight and obese (body mass index 27-37.0 kg/m(2)) predominantly white (98%) women (66%) and men (34%) with a mean (+/-s.d.) 46.8+/-10.4 years of age were randomized into three treatment groups with three matching placebo groups. Recombinant leptin was administered by subcutaneous injection [10 mg/morning, 10 mg/evening or 20 mg/day (10 mg twice daily)]. Patients were counselled at baseline to reduce dietary intake by 2,100 kJ/day (500 kcal/day), and dietary advice was reinforced every 2-4 weeks. RESULTS: No statistically significant change in body weight occurred with recombinant leptin treatment compared with placebo treatment in any treatment group. No clinically significant adverse effects were observed with the exception of an increase in injection-site reactions in patients treated with recombinant leptin (83%) vs. placebo (36%). CONCLUSIONS: Administration of recombinant leptin to an overweight and obese population, in addition to a mildly energy-restricted diet, was not efficacious in terms of weight loss at the doses and schedules studied. The hypothesis that nocturnal administration of recombinant leptin might have a specific effect on weight loss was not supported.
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